In the aggregate, these findings do not prove that exercise slows PD progression, but a neuroprotective effect is certainly plausible, if not compelling. Ideally, this would be assessed in a prospective clinical trial, with patients with PD randomized to regular aerobic exercise vs a passive intervention. However, this is challenging because of practical issues. First, variations in PD drug therapy and exercise compliance would tend to confound the outcomes. Second, PD progression is slow and patients would need to be followed for long durations, with potential for substantial dropouts. Third, we have no reliable biomarker of PD progression and would have to rely on indirect indices. Hence, we currently are primarily left with indirect evidence, as summarized above. Despite these challenges, clinical trials directed at chronic vigorous exercise as a treatment strategy deserve serious consideration.
Exercise influences on general health, well-being, and limitations.
Exercise benefits for patients with PD should also be viewed from a broader perspective, given the general health influences of exercise. PD tends to develop in seniors, who also have risks of various age-related afflictions that are known to benefit from exercise. This especially includes vascular health, both cardiac and cerebral. Numerous other concurrent medical conditions benefit from vigorous exercise including diabetes mellitus, hypertension, hyperlipidemia, obesity, and osteoporosis.2,e36,e37
In the general population, more vigorous physical activity habits in midlife have been associated with significantly longer survival in prospective analysis, controlling for a variety of covariates.e38
Depressione39 and anxietye40 are common in PD. Meta-analyses of clinical trials in the general population have documented significant improvement in both depressione41 and anxietye42 with physical exercise. Moreover, a greater antidepressant effect has been associated with more vigorous exercise.e43
Unlike medications, side effects from an exercise prescription are very limited. Those with angina or uncompensated major organ failure may not be good exercise candidates, and medical clearance from a medical specialist would be advisable for such patients. Certain exercise routines may predispose to falls; hence, patients with imbalance will need to choose exercises that minimize such risks. Beyond this, exercise side effects primarily relate to orthopedic injuries, except for those susceptible to an unsuspected cardiac dysrhythmia. On balance, given the benefits of exercise, the implications for clinicians treating patients with PD are clear.
Exercise as a specific treatment for PD.
This overall body of evidence suggests that vigorous exercise should be accorded a central place in our treatment of PD. It should be encouraged and emphasized as potential strategy for a more favorable disease course. There are 2 fundamental components to this strategy.
First, clinicians should specifically counsel patients with PD to engage in regular exercise, sufficient to establish and maintain physical fitness. The choice of exercise should not only be tailored to the patient's capabilities, but also their interests, so that they will be motivated to maintain a regular routine. Physicians may utilize physical therapists to design programs for deconditioned patients who need a graduated program. The instructions to the physical therapy team should be clear in stating a goal of physical fitness, beyond simply stretching, gait training, and balance exercises. Although age-related orthopedic conditions may limit some activities, the array of exercise equipment in local gyms and health centers allow many exercises tailored to such problems, including machines where exercises are done while seated.
In recent years, a variety of exercise routines have been publicized, such as bicycling/tandem bicycling or vigorous dancing. The literature summarized above does not intuitively endorse any one specific type of exercise, but rather vigorous exercise in general. Any routine ultimately leading to physical fitness should be beneficial.
Second, clinicians must facilitate exercise by appropriately aggressive use of PD drugs. Over the last 2 decades, very conservative symptomatic medical treatment has often been advised, “saving” the best PD treatments for later and arbitrarily limiting dosage. There is no compelling evidence that medication responses can be saved for years later, and similarly there is no good evidence that low doses convey some beneficial effect in the long term. Rather, this approach may translate into lost opportunities. A reasonable goal when prescribing PD medications is to maximize patients' capabilities to engage in physical activities and potentially achieve the best level of physical fitness possible.
Perhaps we have already seen evidence of the benefits of physical activity for PD in the mortality statistics published shortly after levodopa was introduced 4 decades ago. All 8 independent studies comparing longevity immediately before to just after levodopa availability documented substantially improved lifespans.e44-e51 Although this might reflect some neuroprotective effect of levodopa, per se, it is more likely reflective of mobilizing a generation of sedentary patients with PD. There may be a lesson in this early experience from the beginning of the levodopa era: mobilization and physical activity should not be underestimated in the treatment of PD.